INmune Bio, Inc. (NASDAQ: INMB) is a clinical-stage immunotherapy company developing products that modulate the human innate immune system to treat cancer and chronic inflammation. The company's neurodegeneration program centers on XPro1595, a novel dominant-negative TNF-alpha (dnTNF) inhibitor designed to selectively neutralize the neurotoxic soluble form of TNF-alpha while preserving the beneficial membrane-bound form. This approach targets the JAK-STAT and NF-κB signaling pathways implicated in Parkinson's disease neuroinflammation, offering a differentiated mechanism from broad immunosuppressants.
| Attribute | Details |
|---|---|
| Headquarters | Boca Raton, Florida, USA |
| Founded | 2015 |
| CEO | Dr. Raymond J. Kelleher Jr., MD, PhD |
| Ticker | NASDAQ: INMB |
| Employees | ~20 |
| Market Cap | ~$50 million (2024) |
XPro1595 is a next-generation TNF inhibitor that represents a significant advance over first-generation anti-TNF therapies like etanercept and infliximab:
Key Differentiation:
Mechanism of Action:
Connection to JAK-STAT Signaling:
| Attribute | Details |
|---|---|
| Target | Soluble TNF-alpha (neuroinflammation) |
| Mechanism | Dominant-negative inhibitor; modulates JAK-STAT via TNF reduction |
| Phase | Phase 2 |
| Trial ID | NCT04472052 |
| Indication | Parkinson's disease |
| Administration | Subcutaneous injection (weekly) |
A Phase 1 dose-escalation study evaluated the safety, tolerability, and pharmacodynamics of XPro1595 in patients with mild-to-moderate Parkinson's disease[2]:
Key Findings:
The Phase 2 trial (NCT04472052) is a randomized, double-blind, placebo-controlled study in patients with early-stage Parkinson's disease:
| Attribute | Details |
|---|---|
| Phase | Phase 2 |
| Trial ID | NCT05318976 |
| Status | Recruiting |
AD represents a parallel indication where neuroinflammation driven by TNF-alpha and JAK-STAT signaling contributes to disease progression. The Phase 2 AD trial follows the same mechanistic rationale as the PD program.
TNF-alpha is elevated in the brains and CSF of patients with Parkinson's disease and Alzheimer's disease[3]:
First-generation TNF inhibitors (used in autoimmune disease) block both soluble and membrane-bound TNF. This broad blockade:
XPro1595's selective approach may offer a superior safety and efficacy profile for chronic neurodegeneration indications[4].
The JAK-STAT pathway in PD is activated by multiple cytokines including TNF-alpha, IL-6, IL-1β, and IFN-γ. XPro1595 modulates this network by:
| Company | Drug | Target | Stage | Mechanism |
|---|---|---|---|---|
| INmune Bio | XPro1595 | Soluble TNF | Phase 2 (PD/AD) | dnTNF inhibitor; upstream of JAK-STAT |
| Eli Lilly | Baricitinib | JAK1/JAK2 | Phase 2 (PD) | Direct JAK inhibitor |
| Neuraly | NLY01 | GLP-1R | Phase 2 (PD) | Astrocyte modulation (indirect anti-inflammatory) |
Neurotoxic A1 astrocytes are induced by activated microglia via complement cascade. Nature. 2017. ↩︎
INmune Bio announces results from Phase 1 trial of XPro1595 in Parkinson's disease. Movement Disorders. 2022. ↩︎
Targeting neuroinflammation in Parkinson's disease: from mechanisms to clinical trials. Nature Reviews Neurology. 2024. ↩︎
TNF-alpha targeting in neurodegenerative disease. Journal of Neuroinflammation. 2023. ↩︎